Comparison of the TEMPO binocular perimeter and Humphrey field analyzer

This study compared between TEMPO, a new binocular perimeter, with the Humphrey Field Analyzer (HFA). Patients were tested with both TEMPO 24–2 Ambient Interactive Zippy Estimated by Sequential Testing (AIZE)-Rapid and HFA 24–2 Swedish Interactive Threshold Algorithm (SITA)-Fast in a randomized sequence on the same day. Using a mixed-effects model, visual field (VF) parameters and reliability indices were compared. Retinal nerve fiber layer (RNFL) thickness was measured using Cirrus optical coherence tomography (OCT), and coefficient of determinations for VF and OCT parameters were calculated and compared using Akaike information criteria. 740 eyes (including 68 healthy, 262 glaucoma suspects, and 410 glaucoma) of 370 participants were evaluated. No significant differences were seen in mean deviation and visual field index between the two perimeters (P > 0.05). A stronger association between VF mean sensitivity (dB or 1/L) and circumpapillary RNFL was found for TEMPO (adjusted R2 = 0.25; Akaike information criteria [AIC] = 5235.5 for dB, and adjusted R2 = 0.29; AIC = 5200.8 for 1/L, respectively) compared to HFA (adjusted R2 = 0.22; AIC = 5263.9 for dB, and adjusted R2 = 0.22; AIC = 5262.7 for 1/L, respectively). Measurement time was faster for TEMPO compared to HFA (261 s vs. 429 s, P < 0.001). Further investigations are needed to assess the long-term monitoring potential of this binocular VF test.

Glaucoma is an optic neuropathy characterized by the gradual loss of retinal ganglion cells and their axons, which can lead to vision loss 1 .Clinical detection and monitoring of glaucoma involves the assessment of functional vision loss using visual field (VF) testing, and also measuring structural loss through optical coherence tomography (OCT) 2 .VF testing demands active participation from patients and presents several challenges such as lengthy test durations and high variability due to its subjective nature 3 .TEMPO, formally called IMOvifa, is a novel standard automated perimeter with binocular random testing [4][5][6] .Recent studies have suggested that binocular VF testing may effectively suppress eye movements and stabilize fixation, thus potentially enhancing the reliability of test results 7 .Moreover, this device also adjusts the stimulus presentation point by tracking eye movements 6,8,9 .
We hypothesized that this new technology could reduce testing duration and patient fatigue, minimize variability in test results, and improve the correlation between structural and functional data.The purpose of this study was to compare the TEMPO with the Humphrey field analyzer (HFA), the most widely used automated perimeter.1.
A stronger non-linear (dB and μm) association between VF MS and circumpapillary retinal nerve fiber layer (RNFL) thickness was found for TEMPO (adjusted R 2 = 0.25; Akaike information criteria [AIC] = 5235.5)compared to HFA (adjusted R 2 = 0.22; AIC = 5263.9).A similar trend was confirmed for the linear (1/L and μm) relationship (adjusted R 2 = 0.29; AIC = 5200.8for TEMPO, and adjusted R 2 = 0.22; AIC = 5262.7 for HFA, respectively).Moreover, TEMPO demonstrated higher structure-function relationships compared to HFA in     www.nature.com/scientificreports/all quadrants (Table 3).In the non-linear relationship, the inferior quadrant for RNFL had the highest association, followed by superior, temporal, and nasal quadrant for RNFL (adjusted R 2 = 0.31, 0.29, 0.15, and 0.06 for TEMPO, respectively).In contrast, the linear relationship generally showed higher R 2 values compared to nonlinear relationship (adjusted R 2 = 0.49, 0.43, 0.15, and 0.03 for TEMPO, respectively).Figure 2 illustrates the structure-function relationship between global VF MS from TEMPO and HFA, expressed in dB scale (A and B) and unlogged 1/L scale (C and D), and cpRNFL thickness.Supplemental Fig. 2 provides a summary of the usability findings.73% of participants preferred TEMPO, while 17% preferred HFA.83% of participants reported no difficulties with TEMPO.Furthermore, TEMPO received positive feedback in terms of screen readability, ease of concentration, and shorter test duration, as compared to HFA.

Table 3.
Comparison of topographic structure-functional relationship between TEMPO and Humphrey field analyzer.AIC Akaike information criteria, HFA Humphrey field analyzer, RNFL retinal nerve fiber layer, MS mean sensitivity.Age was adjusted in all models.*To compare the strength of structure-function relationship between HFA and TEMPO, the absolute value of the residuals from each model were calculated and compared using mixed effects model.

Discussion
In this study, we prospectively performed VF testing with both TEMPO AIZE-Rapid and HFA Swedish Interactive Threshold Algorithm (SITA)-Fast in a randomized order and identified a stronger structure-function relationship and better reliability indices with TEMPO compared to HFA.TEMPO reduced measurement time by approximately 40% without compromising perimetric performance.Even though the participants were inexperienced with TEMPO prior to the study, it was strongly preferred by patients.
Effective glaucoma management necessitates functional and structural exams, and correlating these changes ensures reliable tracking of disease progression 10,11 .Clinicians should optimize and balance considerations such as medical burden, patient preferences, and efficient detection of disease progression to prevent lifelong visual loss.Previous studies have shown that using a combination of structural and functional analyses enhances the ability to detect glaucoma and its progression [12][13][14] .The current cross-sectional study shows that TEMPO had a stronger structure-function relationship with Cirrus OCT compared to HFA, both globally and sectorally.Our findings support the study by Bowd et al., investigating structure-function relationships using Stratus OCT.They found stronger associations (R 2 = 0.33-0.38) in the inferotemporal disc, followed by modest associations in the superotemporal disc area (R 2 = 0.19-0.25),and weak associations in the temporal disc area (R 2 = 0.02-0.03) 15.The lower structure-function relationship in the temporal quadrants, compared to the superior/inferior quadrants, may be attributed to two factors: the higher variability caused by relatively fewer measurement points for visual field and the position of the optic nerve head in relation to the fovea 16 .Individual anatomical differences, such as variations in the shape, rotation, and tilt of the ONH, can affect the results of structure-function relationship 10 .Both VF and OCT measurements are prone to inter-subject and test-retest variability, which are major causes of discrepancy in structure-function relationship 10,17 .Short-term and long-term reproducibility for TEMPO need to be confirmed in future studies.
The average differences in MD, PSD, and VFI between TEMPO and HFA were all within 1 dB.While the mean difference between the measurements was minimal, we observed a trend where the difference increased with the severity of glaucoma (see Supplemental Fig. 1).This suggests the presence of a proportional bias between the two methods.However, the slope of this trend was not steep, indicating that the increase in difference was moderate relative to the increase in glaucoma severity.In the point-by-point analysis, TEMPO showed a higher sensitivity for total deviation at the points closer to the center.This could be due to the inhibitory responses that occur with the non-occluded eye with HFA 5,18 or, possibly, due to differences in the algorithm used with AIZE 19 .However, the trend was consistent with previously reported data 4 .
HFA SITA-Fast and TEMPO AIZE-Rapid have several items in common regarding reliability indices, but there are some differences.First, false positives are calculated by both devices using reaction time.HFA SITA-Fast uses the percentage of stimuli responded to within a minimum reaction time with an adjustment for the average reaction time of the individual patient 20 .In contrast, TEMPO AIZE-Rapid uses the percentage of those that have a reaction time of less than 0.3 s.Second, false negatives are calculated as percentage of not responding by presenting a 9 dB bright target to the determined threshold in HFA SITA-Fast, while TEMPO AIZE-Rapid uses percentage of not responding by presenting ≥ 2 dB bright target in the process of threshold determination for all stimuli.Third, fixation loss is calculated as percentage in response to stimulus to blind spots, which is known as Heijl Krakau method, in HFA SITA-Fast.In contrast, TEMPO AIZE-Rapid uses the percentage of stimuli with Gaze tracking greater than 5 degrees.Although the Heijl-Krakau method was introduced in the 1970s and is considered the gold standard 21 , it has several disadvantages that include time-consuming catch trials, infrequent fixation check, and inaccuracy of fixation loss ratio when the blind spot location is dislocated.In principle, gaze tracking, which monitors the movement of the pupils, should be expected to measure fixation monitoring more accurately, and also is used in HFA SITA-Faster 22 .In the current study, TEMPO AIZE-Rapid demonstrated lower values than HFA SITA-Fast for all reliability indices.While it's not appropriate to directly compare these indices due to inherent differences in their approaches to reliability, the reduced testing time with TEMPO may be due to lower variability.We speculate that this could account for the improved structure-function relationships and also the overall higher reliability.In the current study, the manufacturer-recommended limits flagged 17.1% of HFA and 10.6% of TEMPO results as low reliability.Fixation losses were the main cause of low reliability for both perimeters (14.4% for HFA and 8.2% for TEMPO).Previous studies have also identified fixation losses as the primary cause of unreliable VF classifications 23,24 .Comparing these numbers is challenging due to methodological differences, but incorporating more accurate and reliable techniques into future device, while maintaining efficacy, is crucial.
This study has several limitations.First, it was based on participants from a tertiary care academic practice, which could introduce certain biases in socio-economic status, demographics, and severity of disease, which could differ from those of patients treated in other settings.This could potentially restrict the generalizability of our findings.Second, the current software is derived from a database that only consists of data from the Japanese population.Regardless of this limitation, HFA and TEMPO exhibited excellent agreement.Third, certain situations, such as conditions of binocular vision dysfunction like strabismus, anisometropia, nystagmus among others, can render binocular open-eye examinations unfeasible 25 .These conditions were not evaluated in our study.Last, all participants were using TEMPO for the first time, while they had previous experience with HFA.Although learning effects tend to increase the false positive rate for inexperienced examinees 26 , false positives were relatively low for TEMPO in our study.
In conclusion, TEMPO showed a stronger structure-function relationship with Cirrus OCT.Further studies are necessary to evaluate the potential of this binocular VF test for longitudinal monitoring.

Figure 1 .
Figure 1.Comparison of reliability indices between Humphrey Field Analyzer and TEMPO.Density plot represents the distribution of (A) fixation losses, (B) false positives, and (C) false negatives.Vertical lines indicate the manufacturer recommended reliable cutoff values.

Figure 2 .
Figure 2. Scatterplots showing the associations between global visual field mean sensitivity from TEMPO and HFA, expressed in dB scale (A, B) and unlogged 1/L scale (C, D), and circumpapillary retinal nerve fiber layer thickness.

Figure 3 .
Figure 3.A topographic map relating visual field test stimulus locations (left) to OCT-measured retinal nerve fiber layer thickness (right) is shown for a right eye.

Table 1 .
Demographic and baseline clinical characteristics of the participants.MD mean deviation, VF visual field.Values are shown in mean (95% confidence interval), unless otherwise indicated.

Table 2 .
Comparison between TEMPO and Humphrey Field Analyzer categorized by diagnosis.HFA Humphrey Field Analyzer.Values are shown in mean (95% confidence interval), unless otherwise indicated.
a Mixed-effects model.